Elixir Institute of Regenerative Medicine

San Jose, CA, United States

Elixir Institute of Regenerative Medicine

San Jose, CA, United States
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Hantash B.M.,Elixir Institute of Regenerative Medicine
Experimental Dermatology | Year: 2012

Peptides are central to the regulation and modulation of the chemical reactions and biological responses that occur in nature. Many physiological processes are affected by the interactions of these peptides, including cell proliferation and migration, inflammation, melanogenesis, angiogenesis and innate immunity. Thus, biologically active peptides offer a great potential medically and therapeutically. Moreover, the ability to generate synthetic peptides with attention to specifically modulating their pharmacokinetics and properties for increased potency, delivery and stability has spurred much interest in this rapidly growing field of research. In this review, we focus on the therapeutic uses of bioactive peptides as antimicrobials and effectors of neurotransmitter release. We also highlight the advantages and challenges associated with this new technology and discuss methods for improving oligopeptide transdermal delivery. © 2012 John Wiley & Sons A/S.

Hantash B.M.,Elixir Institute of Regenerative Medicine
Experimental Dermatology | Year: 2012

Short sequence amino acids or oligopeptides represent a relatively new and promising area of dermatology. Oligopeptides are defined as peptide sequences ranging from 2 to 20 amino acids. This class of proteins includes potent biologically active compounds, which can modulate various cellular and molecular processes. The medical potential of short sequence peptides was initially characterized many decades ago with the identification of biological mediators such as angiotensin, vasopressin, oxytocin and bradykinin. However, the role of oligopeptides in affecting biological activity within the skin has only recently been explored. Currently, the dermatologic use of protein peptide fragments is a rapidly growing field of research. Recent studies suggest that treatment with various biologically active peptides can result in favourable clinical outcomes such as for the treatment of hyperpigmentation disorders with tyrosinase inhibitors and the use of collagen synthesis modulators to diminish skin laxity. In this review, we explore the roles of biologically active short sequence peptides as potential therapeutics through the modulation of collagen, elastin and melanin synthesis. © 2012 John Wiley & Sons A/S.

Hantash B.M.,Elixir Institute of Regenerative Medicine | Bedi V.P.,Solta Medical | Struck S.K.,Struck Plastic Surgery | Chan K.F.,Solta Medical
Journal of Biomedical Optics | Year: 2010

Despite the emergence of nonablative fractional resurfacing (NFR) as a new therapeutic modality for skin photoaging, little is known about the molecular events that underlie the heat shock response to different treatment parameters. Human subjects are treated with a scanned 1550-nm fractional laser at pulse energies spanning 6 to 40 mJ and a 140-μm spot size. The heat shock response is assessed immunohistochemically immediately through 7 days posttreatment. At the immediately posttreatment time point, we observe subepidermal clefting in most sections. The basal epidermis and dermal zones of sparing are both found to express HSP47, but not HSP72. By day 1, expression of HSP72 is detected throughout the epidermis, while that of HSP47 remains restricted to the basal layer. Both proteins are detected surrounding the dermal portion of the microscopic treatment zone (MTZ). This pattern of expression persists through day 7 post-NFR, although neither protein is found within the MTZ. Immediately posttreatment, the mean collagen denaturation zone width is 50 μm at 6 mJ, increasing to 202 μm at 40 mJ. The zone of cell death exceeds the denaturation zone by 19 to 55% over this pulse energy range. The two zones converge by day 7 posttreatment. © 2010 Society of Photo-Optical Instrumentation Engineers.

Reddy B.Y.,UMDNJ New Jersey Medical School | Xu D.S.,Northwestern University | Hantash B.M.,Elixir Institute of Regenerative Medicine
Stem Cells and Development | Year: 2012

Mesenchymal stems cells (MSCs) are a population of multipotent cells residing in several readily available adult tissue compartments, thus allowing for their ex vivo expansion. To date, therapeutic applications of MSCs have focused on their ability to hone to and support the repair of damaged tissues. More recent evidence suggests that MSCs possess low immunogenicity and a diverse array of immunosuppressive properties. In thisarticle, we will review the basic biology of bone marrow-derived MSCs including their immunoregulatory effects and the putative mechanisms underlying them. We will then present some of the recent clinical applications of MSCs that have leveraged these effects for the treatment of immune-mediated dermatoses such as graft-versus-host disease and systemic lupus erythematosus. Although MSCs offer great therapeutic promise, we will also highlight a number of pertinent challenges that should be overcome before their successful clinical translation. © Copyright 2012, Mary Ann Liebert, Inc. 2012.

Ubeid A.A.,Elixir Institute of Regenerative Medicine | Do S.,San Jose State University | Nye C.,San Jose State University | Hantash B.M.,Elixir Institute of Regenerative Medicine
Biochimica et Biophysica Acta - General Subjects | Year: 2012

Background: Abnormal production and accumulation of melanin are characteristics of a number of skin disorders, including postinflammatory hyperpigmentation and melasma. Our objective was to develop and validate novel oligopeptides with potent inhibitory activity against mushroom and human tyrosinase with minimal toxicity toward melanocytes, keratinocytes, and fibroblasts. Methods: A library of short sequence oligopeptides was docked against the crystal structure of mushroom tyrosinase to screen for favorable binding free energies and direct interaction with the catalytic pocket. The inhibitory activity of the octapeptides and hydroquinone (HQ) was assessed using mushroom and human tyrosinase and melanin content via human primary melanocytes. Effects on cell viability and proliferation were determined using the MTT assay and cytotoxicity via trypan blue exclusion. Results: Octapeptides P16-18 outperformed HQ, the benchmark of hypopigmenting agents, in all tested categories. Prolonged incubation of human keratinocytes, fibroblasts, or melanocytes with 30-3000 μM HQ led to 8- to 65-fold greater cell death than with octapeptides. After 6 d of incubation with 30 μM HQ, we observed 70 ± 3% and 60 ± 2% cell death in melanocytes and fibroblasts, respectively, versus minimal toxicity up to an octapeptide concentration of 3 mM. Conclusion: Octapeptides P16-18 are potent competitive tyrosinase inhibitors with minimal toxicity toward the major cell types of human skin. General significance: The findings in our study suggest that all three novel octapeptides may serve as safe and efficacious replacements of HQ for the treatment of pigmentary disorders. © 2012 Elsevier B.V.

Rangarajan S.,University of California at Berkeley | Trivedi A.,San Jose State University | Ubeid A.A.,Elixir Institute of Regenerative Medicine | Hantash B.M.,Elixir Institute of Regenerative Medicine
Lasers in Surgery and Medicine | Year: 2013

Background The sirtuin gene family has been implicated in various anti-senescence pathways. Its connection, if any, with the skin wound healing response has yet to be elucidated. Objective The goal of our study was to better understand the effects of FRF treatment on the sirtuin anti-senescence pathway in skin. Methods Human abdominal skin was treated with FRF, and then harvested at 0, 2, 14, and 28 days post-treatment to assess for temporal changes in gene expression levels. Results Decreased levels of SIRT1, 3, 5, and 7 were observed immediately post-FRF treatment. By Day 2, SIRT1, 6, and 7 expressions increased 50-100%. SIRT6 and 7 expression continued to increase through Day 28. Expression levels of apoptosis genes FoxO3 and p53 decreased, while Bax levels increased by Day 28. Conclusions Our results raise the possibility that sirtuin activity may be used as an accurate corollary to clinical improvement in skin quality. © 2013 Wiley Periodicals, Inc.

Ho J.K.,Stanford University | Hantash B.M.,Elixir Institute of Regenerative Medicine
Expert Review of Dermatology | Year: 2012

Erosive lichen planus (ELP) is an extremely painful condition characterized by ulcerative oral and genital lesions that cause desquamation of the epithelium and bleeding. ELP is more common in women, often recalcitrant to medical therapy and may result in transformation to squamous cell carcinoma. The objective of this review was to assess the evidence in support of various systemic therapies for ELP. PubMed and the Cochrane Database of Systematic Reviews were queried from 1966 to 2009 using the term 'treatment' in combination with 'erosive lichen planus', 'mucosal lichen planus', 'vulvar lichen planus', 'oral lichen planus' or 'vulvovaginal gingival syndrome'. A total of 424 cases, 417 of which met the selection criteria, were identified. Each therapeutic option was scored using the stevens healthcare needs assessment scale for quality and level of evidence, and then weighted based on prevalence of use to arrive at an overall assessment score and rank order. © 2012 Expert Reviews Ltd.

Hantash B.M.,Elixir Institute of Regenerative Medicine | Jimenez F.,Envy Medical Inc.
Journal of Drugs in Dermatology | Year: 2012

Background: Melasma is a cutaneous disorder associated with an overproduction of melanin by the tyrosinase enzyme. A proprietary oligopeptide (Lumixyl™) was previously shown to competitively inhibit mushroom and human tyrosinase in vitro without the associated cytotoxicity of hydroquinone and to diminish the appearance of facial melasma. Objective: The aim of this case study was to determine if the Lumixyl Topical Brightening System (0.01% oligopeptide cream, an antioxidant cleanser, 20% glycolic acid lotion and physical sunscreen) accelerates clearance of mild-to-moderate melasma. Results: All patients showed improvement in their facial melasma with 1 of 4 patients showing complete clearance after just 6 weeks. Conclusions: Results suggest that this regimen may be a useful new tool to treat mild to moderate melasma. Copyright © 2012 Journal of Drugs in Dermatology.

Ball Arefiev K.L.,Stanford University | Hantash B.M.,Elixir Institute of Regenerative Medicine
Dermatologic Surgery | Year: 2012

Background Melasma is an acquired pigmentary disorder classically manifesting as symmetric hyperpigmented macules and patches on the face. It most commonly affects women of reproductive age with darker skin tones but may also affect adolescents, older women, and men. Although its pathogenesis remains unclear, known risk factors include ultraviolet radiation, hormonal variations of pregnancy, thyroid disease, oral contraceptives, and antiseizure medications. Hydroquinone-containing topical agents are the current standard for melasma treatment, but concern about side effects and long-term safety has spurred efforts to develop alternative treatment options. Objectives To review recent advances in melasma treatment. Materials and Methods MEDLINE was searched from 2006 to the present for randomized controlled trials (RCTs) of melasma treatments. Results Nineteen published RCTs were found covering interventions such as topical therapies, chemical peels, and electromagnetic devices. The outcomes of the studies were summarized into tabular form for easy reference and comparison. Conclusions Although melasma is difficult to treat, novel therapeutic modalities have emerged. Further RCT need to be performed to better assess the safety and efficacy of these novel treatment modalities, especially for the long-term maintenance of melasma. © 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.

Elixir Institute Of Regenerative Medicine | Date: 2012-05-10

Disclosed are peptides that inhibit the enzymatic activity of tyrosinase, as well as formulations and methods for their use in the reduction of skin pigmentation, and methods of administering the inhibitory peptides in a topical formulation. Preferred octapeptide sequences are internally rich in tryptophan and/or tyrosine or arginine. The present invention is further directed to kits and compositions containing the present peptides, and methods of treatment of conditions involving expression of tyrosinase, in which the present peptides are administered topically for the treatment of conditions involving melanocyte activity in the skin.

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